The increasing documentation during the past decade of the general similarity of mammalian species, including man, with respect to major and minor histocompatibility antigen systems, immune response genes and the genetic interrelationships of these in some cases, into "complexes" within the genome has encouraged the belief that the rat, as well as the mouse, provides unique experimental material for investigating the peculiarities of cell differentiation that lead to the apparent immunological deficiencies which result in associations of antigen phenotype and predisposition to neoplastic, immune and autoimmune diseases. We have shown that one way in which antigen-associated debilitation develops in rats is via the immune maternal-fetal interactions occurring during pregnancy, frequently severe enough to result in acute or chronic infant mortality, or even prenatal mortality. A major effort of this proposal is to determine the immune bases for these findings, and the long-term immunological consequences to the individual - especially with respect to development of neoplasms, susceptibility to oncogenic virus and predisposition to autoimmunity.